RNF138: E3 Ubiquitin-Protein Ligase RNF138
A key regulator of DNA repair and ubiquitination pathways
Gene Information Card
| Symbol | RNF138 |
|---|---|
| Full Name | Ring Finger Protein 138 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q21.1 |
| NCBI Gene ID | 51444 ncbi.nlm.nih.gov/gene/51444 |
| Ensembl ID | ENSG00000134352 |
| UniProt ID | Q8WVD3 |
| OMIM ID | 616319 |
| HGNC ID | 17271 |
| Aliases | HSD-32, NARF, RNF138, hRNF138, E3 ubiquitin-protein ligase RNF138 |
Description
RNF138 encodes an E3 ubiquitin-protein ligase that plays a critical role in DNA repair, particularly in homologous recombination and non-homologous end joining. It ubiquitinates key DNA repair proteins such as RPA and RAD51, facilitating their recruitment to sites of DNA damage. The protein contains a RING finger domain essential for its ubiquitin ligase activity and is involved in cellular responses to replication stress.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | RNF138 overexpression may promote DNA repair in tumor cells, conferring resistance to therapy | COSMIC, ClinVar |
| Colorectal cancer | Somatic mutations and altered expression observed in tumor samples | COSMIC |
| Fanconi anemia | Potential involvement in the Fanconi anemia pathway via interaction with FANCD2 | UniProt, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone marrow | 10.8 | Medium |
| Lymph node | 8.5 | Medium |
| Brain | 6.3 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 12.5 | High expression in embryonic kidney cells |
| HeLa | 9.8 | Moderate expression in cervical cancer cells |
| MCF7 | 7.3 | Moderate expression in breast cancer cells |
| K562 | 6.1 | Low expression in leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.437C>T (p.Ala146Val) | Missense | 0.01% | Unknown functional impact; reported in ClinVar |
| c.568G>A (p.Glu190Lys) | Missense | 0.005% | Potential loss of ubiquitin ligase activity |
| c.1A>G (p.Met1Val) | Start loss | <0.001% | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the RING domain (e.g., Cys->Ser) impair ubiquitin ligase activity and DNA repair.
Gain of Function (GOF)
Not well characterized; overexpression in some cancers may enhance DNA repair.
Dominant Negative (DN)
Truncating mutations that retain substrate binding but lack catalytic activity may act as dominant negatives.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Homologous recombination (Reactome: R-HSA-5693568)
• Non-homologous end joining (Reactome: R-HSA-5693571)
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
Protein Summary
RNF138 is a 232-amino acid E3 ubiquitin-protein ligase containing a RING-type zinc finger domain. It localizes to the nucleus and is involved in the ubiquitination of DNA repair factors such as RPA and RAD51. The protein promotes efficient homologous recombination and is essential for cellular resistance to DNA-damaging agents. Its expression is highest in testis and bone marrow, suggesting a role in proliferative tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF138 Knockout HEK293 Cell Line | EDJ-KQ10397 | Human | 51444 | Details Get a Quote |
| RNF138 Knockout A-549 Cell Line | EDJ-KQ39049 | Human | 51444 | Details Get a Quote |
| RNF138 Knockout HCT 116 Cell Line | EDJ-KQ39051 | Human | 51444 | Details Get a Quote |
| RNF138 Knockout HeLa Cell Line | EDJ-KQ39052 | Human | 51444 | Details Get a Quote |
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